title: Parenteral nutrition impairs lymphotoxin β receptor signaling via NF-κB.
abstract: OBJECTIVE
  To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin β receptor (LTβR) stimulation in PN animals, and (3) exogenous LTβR blockade in chow animals on NF-κB activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10.
  
  
  BACKGROUND
  LT stimulates LTβR in Peyer's patches (PP) to activate NF-κB via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producing MAdCAM-1, cytokines, and chemokines important in cell trafficking. TNFα, IL-1β, and bacterial products stimulate the inflammatory canonical NF-κB pathway producing p65/p50 and c-Rel/p50. PN decreases LTβR, MAdCAM-1, and chemokines in PP and lowers small intestinal IgA compared with chow.
  
  
  METHODS
  Canonical (p50 and p65) and noncanonical (p52 and Rel B) NF-κB proteins in PP were analyzed by TransAM NF-κB kit after 5 days of chow or PN, 2 days of LTβR stimulation or 3 days of LTβR blockade. MAdCAM-1, chemokines, and cytokines in PP were measured by ELISA after LTβR stimulation or blockade.
  
  
  RESULTS
  PN significantly reduced all NF-κB proteins in PP compared with chow. Exogenous LTβR stimulation during PN increased p50, p52, Rel B, MAdCAM-1, IL-4, and IL-10 in PP, but not p65, CCL19, CCL20, or CCL25 compared with PN. LTβR blockade reduced noncanonical products (p52 and Rel B), MAdCAM-1, CCL19, CCL20, CCL25, IL-4, and IL-10 but had no effect on the inflammatory pathway (p50 and p65) compared with chow.
  
  
  CONCLUSIONS
  Lack of enteral stimulation during PN decreases both canonical and noncanonical NF-κB pathways in PP. LTβR stimulation during PN feeding completely restores PP noncanonical NF-κB activity, MAdCAM-1, IL-4, IL-10, and partly the canonical pathway. LTβR blockade decreases the noncanonical NF-κB activity, MAdCAM-1, chemokines, and cytokines without effect on the canonical NF-κB activity in PP.
authors.affiliation: Surgical Service, William S. Middleton Memorial Veterans Hospital, Madison WI, USA.
authors.forename: Jinggang
authors.initials: J
authors.lastname: Lan
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sano
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jonker
authors.forename: Jiro
authors.initials: J
authors.lastname: Omata
authors.forename: Wentong
authors.initials: W
authors.lastname: Xu
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015815:Cell Adhesion Molecules; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009088:Mucoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000009:adverse effects* / Q000379:methods; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D007136:Immunoglobulins; D053259:Lymphotoxin beta Receptor; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D016328:NF-kappa B; D016753:Interleukin-10; D015847:Interleukin-4